The pathogenicity for mice of ecotropic and MCF-type recombinant murine C-type viruses (MuLV) and of recombinant viruses constructed in vitro is under study. Two ecotropic viruses from wild mice, C2S-M and CasBr-M, have been found to induce an unusual array of hematopoietic neoplasms in NFS mice inoculated as newborns. Several replication competent MCF viruses as well as two defective rapidly oncogenic viruses have been isolated from tumors of various types and are being characterized for pathogenicity, effects of host genetic influences, and restriction enzyme patterns. For studies designed to test directly the role of those portions of MuLV genomes which have been found to differ regularly between viruses with differing capacities to induce disease, in vitro recombinants were prepared from restriction enzyme fragments of molecularly cloned leukemogenic AKR MCF 247 virus and non-leukemogenic AKR ecotropic virus. Similarly, recombinant viruses were derived from cloned Moloney MuLV, which induces lymphoblastic lymphoma, and Friend MuLV, which induces erythroleukemia. Results of pathogenicity testing of these recombinant viruses indicate that control signals in the LTR region of the genome are critical in determining target cell-specificity in the Friend-Moloney system, and play a role in MCF 247-induced acceleration of AKR thymic lymphoma. In the latter case, nucleotide sequences in the env region, including segments coding for both gp70 and pl5E, also contribute signficantly to the leukemogenic phenotype.